Central neurotoxicity of cyclosporine in two children with nephrotic syndrome

Abstract

The central neurotoxicity of cyclosporin A (CsA) has been abundantly documented in pediatric and adult recipients of bone marrow or organ transplants, with variations in the rate of occurrence from 0.5% to 35%. We report two cases of central neurotoxicity ascribable to CsA in children with nephrotic syndrome due to lipoid nephrosis. The manifestations of CsA-related central neurotoxicity include confusion, aphasia, dystonias, akinetic mutism, parkinsonism, palsies, seizures, catatonia, coma, brain hemorrhage, and cortical blindness. Decreased density of the cerebral white matter is visible by computed tomography (CT) in 50% of cases, with the most commonly involved sites being the occipital cortex, the cerebellum, the periventricular substance, and the brainstem. Magnetic resonance imaging is more sensitive and more specific than CT for investigating the white matter. High-signal lesions are seen on T2-weighted sequences in the areas that are abnormal by CT. Many risk factors have been reported, including hypomagnesemia, hypocholesterolemia, high-dose glucocorticoid therapy, arterial hypertension, and infections. We present two patients with central neurotoxicity both of whom have elevated cholesterol levels.

Pseudotumor cerebral associado ao uso de ciclosporina após transplante renal

“…14 Neurological effects secondary to the use of CsA may occur in 0.5% to 35% of the patients and comprise trembling, paresthesias, paralyses, confusion, lethargy, depression, anxiety, insomnia, hallucinations, convulsions, aphasia, mutism. 2,18 Headache is a common complaint and may end up simulating migraine and hypertensive encephalopathy. Thus, attention should be paid to unspecific complaints, especially when accompanied by visual alterations.…”

BRAIN CYCLOSPORIN A LEVELS ARE DETERMINED BY ONTOGENIC REGULATION OFMDR1AEXPRESSION

“…Use of calcineurin inhibitors (CyA and tacrolimus) for suppression of organ rejection in pediatric renal transplant patients can precipitate CNS toxicity, behavioral disturbances, and interruptions in immunosuppressive therapy (Awan et al, 1999;Parvex et al, 2001;Yamauchi et al, 2002;Taque et al, 2004). Approximately 10% to 15% of pediatric renal transplant patients will exhibit significant clinical CNS toxicity characterized by post-transplant seizures (Awan et al, 1999).…”

“…CyA is used extensively as an immunosuppressant agent in pediatric solid organ transplant recipients (Hoyer and Vester, 2004;Pape et al, 2004) and can produce serious toxic side effects including nephrotoxicity and neurotoxicity, which can hinder successful immunotherapy and adversely affect pediatric patient health (Jeruss et al, 1998;Pape et al, 2004;Taque et al, 2004). Based on this clinical/ toxicological relevance in pediatric drug therapies, CyA was chosen as our primary substrate for the mdr1a functional studies.…”

Reversible posterior leukoencephalopathy syndrome in children undergoing induction therapy for acute lymphoblastic leukemia

“…Scattered case studies have reported RPLS in children undergoing therapy for cancer, 8,10,11 although it is still not widely recognized as a potential complication of chemotherapy. Reports prior to description of the entity and more advanced imaging techniques also described cortical blindness in children receiving vincristine, cyclosporine, or other immunosuppressive agents 12–15. In this report, we include three patients undergoing induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) who present with clinical and radiological findings of RPLS.…”